We have developed and patented (U.S. Pat No. 5,706,830) a new type of closed circuit perfluorocarbon (PFC) liquid ventilator with enhanced capabilities for gas exchange and exudates clearance from the lungs. This system has potential application to rescue of patients in acute respiratory failure and treatment of cystic fibrosis. The system employs a continuous isovolumetric perfusion (bias flow) of oxygenated PFC through one lumen of a double lumen endotracheal catheter that is superimposed on tidal liquid ventilation (liv). Phase I studies in newborn piglets indicate that bias flow significantly improved blood gases and increased the clearance of a five percent albumin solution from the lung by over 3-fold. During Phase II we propose to finalize the prototype design and control system software for ventilatory parameters and a feedback control of lung liquid volume based on measurements of end-expiratory stop-flow pressures. High performance pulseless pumps, an oxygenator and vapor recovery system will be included as well as protective algorithms and relief valves to limit airway pressure excursions. Phase II experimental studies in piglets and rabbits will examine novel applications of TLV with bias flow for sustaining arterial blood gases during oleic acid lung injury, increasing the clearance rate of five percent albumin solution and mucus-like gels from the lung, and enhancing the homogeneity of gene expression for a reporter gene introduced during TLV. We will also apply for an Investigational Device Exemption (IDE) from the Food and Drug Administration during Phase II to distribute ventilator prototypes to research institutions. PROPOSED COMMERCIAL APPLICATION: This liquid ventilator will be used in infant and adult intensive care units to treat end-stage respiratory failure as a lower cost alternative to extracorporeal oxygenation. Other applications include continuous intrapulmonary administration of drugs and anesthetics and clearance of material from the lungs.